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https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#1
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29340775/global-versus-local-mechanisms-of-temperature-sensing-in-ion-channels
#2
REVIEW
Cristina Arrigoni, Daniel L Minor
Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29336091/drug-resistance-in-anaplastic-lymphoma-kinase-rearranged-lung-cancer
#3
Ryohei Katayama
The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induce abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation...
January 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29331865/structure-based-assessment-of-protein-protein-interactions-and-accessibility-of-protein-ix-in-adenoviruses-with-implications-for-antigen-display
#4
Nathaniel L Matteson, Michael A Barry, Vijay S Reddy
The exterior minor protein IX of adenoviruses (AdVs) is a frequent target of attachment of antigens and the modified AdVs are being used as potent vaccine platforms. The organization of protein IX is disticntly different between human adenoviruses (HAdVs) and non-HAdVs. The analysis of solvent accessibility, based on the near atomic resolution structures, suggests that the C-terminal residues of IX are more accessible in non-HAdVs (e.g., bovine adenovirus) than in HAdVs. Although the C-terminal fusions of IX are displayed on the capsid surface, they could disrupt the formation of tetrameric coiled-coils (4-HLXB) in HAdVs due to steric hinderance, thereby potentially affecting the capsid stability...
January 11, 2018: Virology
https://www.readbyqxmd.com/read/29325713/the-interaction-of-tak1-and-tab1-enhances-lps-induced-cytokine-release-via-modulating-nf-%C3%AE%C2%BAb-activation-larimichthys-crocea
#5
Shi-Yuan Bao, Qing-Xue Sun, Cui-Luan Yao
Transforming growth factor-β-activating kinase 1 (TAK1) is triggered by foreign pathogenic infection and involves in proinflammatory response through the activation of nuclear factor-κB (NF-κB), which is specifically regulated by TAK1-binding protein 1 (TAB1). However, the expression and regulatory characterizations of TAK1 and TAB1 in fish immune response remain largely unknown. In the present study, the cDNA sequences of TAK1 (LcTAK1) and TAB1 (LcTAB1) were identified from large yellow croaker, Larimichthys crocea...
January 8, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29323635/mukb-atpases-are-regulated-independently-by-the-n-and-c-terminal-domains-of-mukf-kleisin
#6
Katarzyna Zawadzka, Pawel Zawadzki, Rachel Baker, Karthik V Rajasekar, Florence Wagner, David J Sherratt, Lidia K Arciszewska
The Escherichia coli SMC complex, MukBEF, acts in chromosome segregation. MukBEF shares the distinctive architecture of other SMC complexes, with one prominent difference; unlike other kleisins, MukF forms dimers through its N-terminal domain. We show that a 4-helix bundle adjacent to the MukF dimerization domain interacts functionally with the MukB coiled-coiled 'neck' adjacent to the ATPase head. We propose that this interaction leads to an asymmetric tripartite complex, as in other SMC complexes. Since MukF dimerization is preserved during this interaction, MukF directs the formation of dimer of dimer MukBEF complexes, observed previously in vivo...
January 11, 2018: ELife
https://www.readbyqxmd.com/read/29321961/biophysical-characterization-of-atg11-a-scaffold-protein-essential-for-selective-autophagy-in-yeast
#7
Hironori Suzuki, Nobuo N Noda
Autophagy is an intracellular degradation system in which the formation of an autophagosome is a key event. In budding yeast, autophagosomes are generated from the preautophagosomal structure (PAS), in which Atg11 and Atg17 function as scaffolds essential for selective and nonselective types of autophagy, respectively. Structural studies have been extensively performed on Atg17, but not on Atg11, preventing us from understanding the selective type of the PAS. Here, we purified and characterized Atg11. Biophysical analyses, including analytical ultracentrifugation and CD, showed that Atg11 behaves as an elongated homodimer abundant in α-helices in solution...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321952/fasciculation-and-elongation-zeta-1-protein-fez1-interacts-with-the-retinoic-acid-receptor-and-participates-in-transcriptional-regulation-of-the-hoxb4-gene
#8
Mariana Bertini Teixeira, Ana Carolina M Figueira, Ariane S Furlan, Bruno Aquino, Marcos R Alborghetti, Adriana F Paes Leme, Li-Na Wei, Jörg Kobarg
Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1-RAR interaction...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29319354/inhibition-of-the-rhoa-rho-associated-coiled-coil-containing-protein-kinase-1-pathway-is-involved-in-the-therapeutic-effects-of-simvastatin-on-pulmonary-arterial-hypertension
#9
Wei-Hua Liu, Xiao-Hong Xu, Qin Luo, Hong-Liang Zhang, Yong Wang, Qun-Ying Xi, Zhi-Hui Zhao, Zhi-Hong Liu
BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i...
January 10, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29317535/structural-basis-of-stat2-recognition-by-irf9-reveals-molecular-insights-into-isgf3-function
#10
Srinivasan Rengachari, Silvia Groiss, Juliette M Devos, Elise Caron, Nathalie Grandvaux, Daniel Panne
Cytokine signaling through the JAK/STAT pathway controls multiple cellular responses including growth, survival, differentiation, and pathogen resistance. An expansion in the gene regulatory repertoire controlled by JAK/STAT signaling occurs through the interaction of STATs with IRF transcription factors to form ISGF3, a complex that contains STAT1, STAT2, and IRF9 and regulates expression of IFN-stimulated genes. ISGF3 function depends on selective interaction between IRF9, through its IRF-association domain (IAD), with the coiled-coil domain (CCD) of STAT2...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29317443/a-mutation-in-ccdc39-causes-neonatal-hydrocephalus-with-abnormal-motile-cilia-development-in-mice
#11
Zakia Abdelhamed, Shawn M Vuong, Lauren Hill, Crystal Shula, Andrew Timms, David Beier, Kenneth Campbell, Francesco T Mangano, Rolf W Stottmann, June Goto
Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia...
January 9, 2018: Development
https://www.readbyqxmd.com/read/29316146/modifying-the-sterics-in-the-second-coordination-sphere-of-designed-peptides-leads-to-enhancement-of-nitrite-reductase-activity
#12
Karl Koebke, Fangting Yu, Elvin Salerno, Casey Van Stappen, Alison Tebo, James Penner-Hahn, Vincent Louis Pecoraro
Protein design is a useful strategy to interrogate the protein structure-function relationship. We demonstrate using a highly modular 3-stranded Coiled Coil (TRI-peptide system) that a functional type 2 copper center exhibiting copper nitrite reductase (NiR) activity exhibits the highest homogeneous catalytic efficiency under aqueous conditions for the reduction of nitrite to NO and water. Modification of the amino acids in the second coordination sphere of the copper center increases the nitrite reductase activity up to 75-fold compared to previously reported systems...
January 8, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29315927/the-major-effect-qtl-csarn6-1-encodes-an-aaa-atpase-domain-containing-protein-that-is-associated-with-waterlogging-stress-tolerance-through-promoting-adventitious-root-formation
#13
Xuewen Xu, Jing Ji, Qiang Xu, Xiaohua Qi, Yiqun Weng, Xuehao Chen
In plants, the formation of hypocotyl-derived adventitious roots (AR) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL ARN6.1 that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that the CsARN6...
January 8, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29315863/activatable-protein-nanoparticles-for-targeted-delivery-of-therapeutic-peptides
#14
Xi Yu, Xingchun Gou, Peng Wu, Liang Han, Daofeng Tian, Fengyi Du, Zeming Chen, Fuyao Liu, Gang Deng, Ann T Chen, Chao Ma, Jun Liu, Sara M Hashmi, Xing Guo, Xiaolong Wang, Haitian Zhao, Xinran Liu, Xudong Zhu, Kevin Sheth, Qianxue Chen, Louzhen Fan, Jiangbing Zhou
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29313410/ulk1-phosphorylates-ser30-of-becn1-in-association-with-atg14-to-stimulate-autophagy-induction
#15
Ji-Man Park, Minchul Seo, Chang Hwa Jung, Douglas Grunwald, Matthew Stone, Neil Michael Otto, Erik Toso, Yeseul Ahn, Michael Kyba, Timothy J Griffin, LeeAnn Higgins, Do-Hyung Kim
ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine kinase that plays a key role in regulating macroautophagy/autophagy induction in response to amino acid starvation. Despite the recent progress in understanding ULK1 functions, the molecular mechanism by which ULK1 regulates the induction of autophagy remains elusive. In this study, we determined that ULK1 phosphorylates Ser30 of BECN1 (beclin 1) in association with ATG14 (autophagy related 14) but not with UVRAG (UV radiation resistance associated)...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29310791/matrilins
#16
Mats Paulsson, Raimund Wagener
Marilins mediate interactions between macromolecular components of the extracellular matrix, e.g., collagens and proteoglycans. They are composed of von Willebrand factor type A and epidermal growth factor-like domains and the subunits oligomerize via coiled-coil domains. Matrilin-1 and -3 are abundant in hyaline cartilage, whereas matrilin-2 and -4 are widespread but less abundant. Mutations in matrilin genes have been linked to chondrodysplasias and osteoarthritis and recently characterization of matrilin-deficient mice revealed novel functions in mechanotransduction, regeneration, or inflammation...
2018: Methods in Cell Biology
https://www.readbyqxmd.com/read/29299747/gdc-0152-induced-autophagy-promotes-apoptosis-in-hl-60-cells
#17
Liang Peiqi, Hu Rong, Dong Hongming, Liu Zhuogang, Jiang Wei, Miao Miao
GDC-0152 is a new type of chemical compound which can downregulate inhibitor of apoptosis protein. We previously reported that GDC-0152 induced apoptosis in HL-60 cells in a caspase-dependent manner. In this study, we have focused on GDC-0152-induced autophagy and the relationship between apoptosis and autophagy. We found that GDC-0152 can evoke autophagy flux as confirmed by the upregulation of LC3 and downregulation of p62. The conversion of LC3I to LC3II verified the existence of autophagy flux further. GDC-0152 induced autophagy through downregulating B cell lymphoma 2 and Bcl-2-interacting myosin-like coiled-coil protein, and upregulating WD-repeat domain phosphoinositide-interacting protein 1...
January 3, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29298434/coiled-coil-formation-conveys-a-stim1-signal-from-er-lumen-to-cytoplasm
#18
Nupura Hirve, Vangipurapu Rajanikanth, Patrick G Hogan, Aparna Gudlur
STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca2+ and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca2+ channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca2+-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca2+ is bound to STIM ER-luminal domains...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29290112/insight-into-the-role-of-the-hv1-c-terminal-domain-in-dimer-stabilization
#19
Panisak Boonamnaj, Pornthep Sompornpisut
The voltage-gated proton-selective channel (Hv1) conducts protons in response to changes in membrane potential. The Hv1 protein forms dimers in the membrane. Crystal structures of Hv1 channels have revealed that the primary contacts between the two monomers are in the C-terminal domain (CTD), which forms a coiled-coil structure. The role of Hv1-CTD in channel assembly and activity is not fully understood. Here, molecular dynamics (MD) simulations of full-length and truncated CTD models of human and mouse Hv1 channels reveal a strong contribution of the CTD to the packing of the transmembrane domains...
January 1, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29284678/the-cue1-domain-of-the-snf2-like-chromatin-remodeler-smarcad1-mediates-its-association-with-krab-associated-protein-1-kap1-and-kap1-target-genes
#20
Dong Ding, Philipp Bergmaier, Parysatis Sachs, Marius Klangwart, Tamina Rückert, Nora Bartels, Jeroen Demmers, Mike Dekker, Raymond A Poot, Jacqueline E Mermoud
Chromatin in embryonic stem cells (ESCs) differs markedly from that in somatic cells, with ESCs exhibiting a more open chromatin configuration. Accordingly, ATP-dependent chromatin remodeling complexes are important regulators of ESC homeostasis. Depletion of the remodeler SMARCAD1, an ATPase of the SNF2 family, has been shown to affect stem cell state, but the mechanistic explanation for this effect is unknown. Here, we set out to gain further insights into the function of SMARCAD1 in mouse ESCs. We identified KRAB-associated protein 1 (KAP1) as the stoichiometric binding partner of SMARCAD1 in ESCs...
December 28, 2017: Journal of Biological Chemistry
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